We are investigating the phenomenon of ectopic synthesis of placental proteins by nontrophoblastic neoplasms because of the link between the mechanisms associated with the derepression of the genes synthesizing embryonic proteins and those involved in neoplastic transformation. Our work has concentrated on two placental membrane proteins with emphasis on alkaline phosphatase (PAP) and the transferrin receptor. We have performed chromosome mapping studies using mouse/human somatic cell hybrids to identify the chromosomal location of the transferrin receptor, P97, an iron-binding protein on melanoma cells, both of which are on chromosome 3, and have made the assignment for a placental membrane protein entitled Troph 4, which has been assigned to chromosome 11. We have investigated the regulation of alkaline phosphatase activity by 1,25 dihydroxyvitamin D3and showed specific activation of the phenotypic bone enzyme. We have characterized the fetal intestinal alkaline phosphatase molecule and have demonstrated that this molecule is a heteromer of both placental and intestinal subunits. The switch from fetal to intestinal form involves the repression of synthesis of the placental subunit and the cessation of sialylation of the intestinal form. We have conducted further studies characterizing the transferrin receptor. We made monoclonal antibodies to purified receptor which react at different sites in the molecule. We showed that the expression of the transferrin receptor is controlled by the intracellular iron concentration. We investigated the effect of endogenous ligand on the association constant for transferrin binding to its receptor; conducted a systematic study characterizing specific binding of transferrin to its receptor; and demonstrated the internalization and recycling of the transferrin-receptor complex using combined biochemical and immunocytological techniques with fluorescence and electron immunomicroscopy. (M)